nitrophenols and Drug-Related-Side-Effects-and-Adverse-Reactions

Levodopa has been the gold standard therapy for the motor symptoms of Parkinson's disease for more than three decades. Although it remains the most effective treatment, its long-term use is associated with motor fluctuations and dyskinesias that can be disabling for patients and difficult for physicians to manage medically. In the last 10 years, the catechol-O-methyltransferase (COMT) inhibitor tolcapone has been studied for its efficacy as an adjunctive treatment to levodopa plus a dopa decarboxylase inhibitor. Adjunctive therapy with tolcapone can significantly reduce the dose of levodopa required. Moreover, treatment with tolcapone significantly reduces wearing off and on-off periods in fluctuating patients and improves 'on' time in patients with stable disease. Tolcapone has assumed a new place in the arsenal of medications for Parkinson's disease. This paper reviews the pharmacology, safety and efficacy of tolcapone in patients with advanced Parkinson's disease. After some initial concerns about its safety, tolcapone has been shown to be safe if used and monitored according to guidelines regarding liver function. Tolcapone produces expected dopaminergic side effects, including headache, nausea, insomnia, as well as diarrhea; however, these side effects are generally mild and as a rule do not result in discontinuation of therapy.

Topics: Antiparkinson Agents; Benzophenones; Drug-Related Side Effects and Adverse Reactions; Humans; Levodopa; Nitrophenols; Parkinson Disease; Tolcapone; Treatment Outcome

Topics: Adverse Drug Reaction Reporting Systems; Antiparkinson Agents; Benzophenones; Chemical and Drug Induced Liver Injury; Drug-Related Side Effects and Adverse Reactions; European Union; Humans; Legislation, Drug; Nitrophenols; Parkinson Disease; Tolcapone

In 1998, the European Medicines Agency suspended the approval for tolcapone in Parkinson's disease (PD) with motor complications due to the drug's implication in fulminant liver failure and the consequent death of 3 patients. Clinical data obtained by ongoing use of tolcapone in other countries proved that adequate safety can be achieved if liver enzymes are strictly monitored. In 2005, tolcapone was relaunched in the European Union under the prerequisite of biweekly liver enzyme monitoring. The objective of this study was to evaluate the compliance with mandatory drug safety monitoring under real-life conditions.. Twenty-one Parkinson's disease patients receiving tolcapone were analyzed with regard to their compliance in performing and reporting the required laboratory tests.. Tolcapone was effective and well tolerated. Yet, less than 25% of the patients regularly performed and reported the required laboratory tests and the compliance declined when comparing the first and second half-years of therapy.. Our data shed light on the incongruity between requirements of postmarketing drug surveillance and every-day reality. The depicted noncompliance is most likely a general problem in postmarketing drug surveillance with an impact for physicians, manufacturers and legal authorities. Practical, legal and ethical aspects will be discussed.

Topics: Adverse Drug Reaction Reporting Systems; Aged; Alanine Transaminase; Antiparkinson Agents; Aspartate Aminotransferases; Benzophenones; Drug Monitoring; Drug-Related Side Effects and Adverse Reactions; European Union; Female; Humans; Male; Middle Aged; Nitrophenols; Parkinson Disease; Patient Compliance; Tolcapone